Nix finished with 308 total yards, three touchdowns, and one interception after playing the entire game.
Denver, who will host either the Houston Texans or New England Patriots next week in the AFC Championship game, will turn to backup quarterback Jarrett Stidham to lead them going forward.
Nix was clutch for the Broncos in their win over the Bills. He hit wide receiver Marvin Mims Jr. for a 29-yard touchdown with 55 seconds left in the game to take a 30-27 lead before the Bills tied it up with a field goal on their ensuing drive.
Denver will be playing in their first AFC Championship game since the 2015 season, when they went on to win the Super Bowl.